Practical ion mobility spectrometer apparatus and methods for chemical and/or biological detection

ABSTRACT

The present invention relates to drift tubes for ion mobility spectrometers. In one embodiment, the drift tube of the present invention uses a simplified design having helical resistive material to form substantially constant electric fields that guide ion movements. The drift tube for ion mobility spectrometers described herein is constructed with a non-conductive structure. This configuration provides a robust ion mobility spectrometer that is simple to build. One feature of the present invention is that the drift tube design described herein enables the ion mobility spectrometer to be built with a lower weight, lower power consumption, lower manufacturing cost, and free of sealants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/38,736 filed on Dec. 19, 2016, which is pending. Application Ser. No.15/38,736 is a continuation in part of U.S. patent application Ser. No.13/083,128, filed on Apr. 8, 2011, now U.S. Pat. No. 8,314,383, which isa Divisional patent of U.S. patent application Ser. No. 11/946,679,filed on Nov. 28, 2007, now U.S. Pat. No. 7,943,901. The presentapplication claims the benefit of and priority to corresponding U.S.Provisional Patent Application 60/867,400 filed Nov. 28, 2006; theentire content of the application is herein incorporated by reference.The contents of all of these patent applications are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

Many chemical and/or biological analytical instruments that arecurrently used for sample analysis have many limitations. Some areasthat are currently deficient are: the ability to quickly analyze asample using a compact instrument in a high throughput manner, anefficient and effective sampling method, and an effective manner tointerface multiple analytical instruments. A comprehensive instrumentalapproach can address chemical and/or biological detection issues in manyareas/applications such as pharmaceutical, environmental, and foodindustry, as well as homeland security, in particular home madeexplosives, liquid detection needs with adaptability to future threats.A comprehensive instrumental approach on ion mobility spectrometer (IMS)apparatus and methods offer all of the following advantages: improvedthroughput compared to current detection systems; adaptability to newionization methods that can be used to introduce samples in differentcategories of chemicals in vapor, liquid and particle forms; enhancedcapability for detecting labile chemicals, such as homemade explosivesTATP, nitroglycerine and PETN; and an interface to mass spectrometers(MS) that will enhance field performance of future MS based fielddetection systems.

Ion mobility based spectrometers need to utilize various methods andcomponents to be able to analyze samples in a high throughput mannerand/or operate in a portable design. Current ion mobility basedspectrometers require complicated mechanically designed parts forconstruction of the drift tube, whereby each component in the drift tuberequires multiple parts and produces an overall high power consumptionsystem. The high power consumption significantly limits the performanceof the ion mobility based spectrometer. One aspect of the presentinvention relates to ion mobility based spectrometer systems forcontinuous sampling operations, rapid temperature control/temperaturegradient analysis, and low power consumption portability.

In practical chemical detection, such as explosive detection,applications, the two major challenges to a given analytical instrumentare system effectiveness and readiness. Even though existing IMS basedtrace detection systems can meet the current throughput requirements atairport checkpoint, these detection systems need to have much higherthroughput in order to handle the detection requirements for masstransit applications.

Ion mobility based spectrometers (IMS) and MS utilize various methods tointroduce the vapor of a sample into the analysis chamber and/orionization chamber of the given instrument. For example liquid samplescan be injected via a syringe and thermally vaporized. Whereas solidsamples are commonly vaporized via thermal desorption. Many differentmethods can be utilized, the chemical nature of the sample generallyinfluences the method used. Heating samples to elevated temperatures inorder to vaporize them can be destructive. Since the currently usedmethods for heating the samples in an IMS range between 220° C. and 300°C., decomposition can occur at these elevated temperatures. For example,the explosive 1,1-diamino-2,2-dinitroethylene (FOX-7) decomposes at 238°C.

The basic components of a typical ion mobility spectrometer (IMS)include an ionization source, a drift tube that includes a reactionregion, an ion shutter grid, a drift region, and an ion detector. In gasphase analysis, the sample to be analyzed is introduced into thereaction region by an inert carrier gas, ionization of the sample isoften accomplished by passing the sample through a reaction regionand/or an ionization region. The generated ions are directed toward thedrift region by an electric field that is applied to drift rings(sometime referred as guard rings or ion guide) that establish the driftregion. A narrow pulse of ions is then injected into, and/or allowed toenter, the drift region via an ion shutter grid. Once in the driftregion, ions of the sample are separated based upon their ionmobilities. The arrival time of the ions at a detector is an indicationof ion mobility, which can be related to ion mass. However, one skilledin the art appreciates that ion mobility is not only related to ionmass, but rather is fundamentally related to the ion-drift gasinteraction potential, which is not solely dependent on ion mass.

State-of-the art ion mobility spectrometers include drift tubes withcomplicated mechanic parts. Each component in the drift tube typicallyrequires the assembly of multiple parts. Such complex mechanical designssignificantly increase the cost of ion mobility spectrometer and canalso limit the performance of the ion mobility spectrometer. In general,the more parts in the drift tube design, then the higher probabilitythat the drift tube will have technical problems, such as gas leakage,inadequate temperature control, inadequate pressure control, thermaland/or electrical insulation leakage.

For many applications, such as explosive detection in highlycontaminated field environments, normal operation of the spectrometer isfrequently prevented by overloading the system with large samples orcontaminants. Rapid self cleaning mechanisms are highly desired forthese applications. Conventional ion mobility spectrometer drift tubeconstructions are described by Ching Wu, et al., “Construction andCharacterization of a High-Flow, High-Resolution Ion MobilitySpectrometer for Detection of Explosives after Personnel PortalSampling” Talanta, 57, 2002, 123-134. The large thermal mass of the tubestructure prevents the system from flash heating and rapid cooling ofthe ion mobility spectrometric components for cleaning purpose.Spectrometric components can be cleaned by “baking out” the components.However, “baking out” typically takes hours to complete.

Previous publications have indicted that a uniform electric field in thedrift region of an ion mobility spectrometer is imperative to achievehigh mobility resolution in such devices. See, for example, Ching Wu, etal., “Electrospray Ionization High Resolution Ion MobilitySpectrometry/Mass Spectrometry,” Analytical Chemistry, 70, 1998,4929-4938. A uniform electric field can be created by reducing the sizeof each voltage drop step and increasing the number of drift rings.Narrow drift rings are utilized to generate the desired fielddistribution. However, the more drift rings that are used in a drifttube, the more lead wires are needed to be sealed at the wall tocomplete the drift tube structure. Structure complication greatly limitsthe possibility of creating highly uniform electric fields in the drifttube. U.S. Pat. No. 4,7120,080 and U.S. Patent Publication No.2005/0211894 A1 describe layers of conductive coating that are commonlyproposed to build the drift tube. However, coatings that are exactly thesame thickness along the drift tube are a very challenging to make.Conductive layers with uneven coating thickness will cause distortedelectric field distributions and unpredictable system performance.

SUMMARY OF THE INVENTION

The present invention generally relates to systems and methods ofanalyzing samples using a chemical and/or biological analyticalinstrument, in particular this invention addresses current issues ofchemcial detection/analysis by developing a comprehensive detectionsystem based on an integrated IMS that could be used for explosivedetection for scenarios under high throughput conditions. Interfacingthe IMS to new ionization methods that can be used to introducedifferent categories of explosives and using the IMS to bridge thesampling system and concept of operations for IMS to MS based detectionsystems, thus enhancing and enabling the fieldablity of MS baseddetectors. The subject matter of the present invention involves, in somecases, interrelated products, alternative solutions to a particularproblem, and/or a plurality of different uses of one or more systemsand/or articles.

In one aspect of the invention, a high throughput trace detector (HTTD,this term sometime is used interchangeable with IMS) is based on highthermal conductivity ion mobility spectrometers (HTCIMS). The uniqueconfiguration of the HTCIMS allows rapid change of detector temperaturethus enabling time-temperature desorption methods and TRUE temperatureramping in the trace detection process. True temperature ramping enableshigher sensitivity and selectivity for thermally labile explosives. Thelow thermal mass construction of the HTCIMS will also allow rapid systemclean up in seconds, which eliminates system down time in highthroughput detection applications. In addition, the low thermal massconstruction allows a lower overall power consumption system that isuseful for portable detection applications. In another set ofembodiments, the invention uses the HTCIMS to eliminate detector memoryeffects and achieve simultaneous temperature ramping of desorber and IMSdetector; this innovative detection system will improve capabilities ofIMS based trace detection systems and provide a device that has higherthroughput and greater detection effectiveness for explosive detection.

In yet another set of embodiments, the IMS system is equipped withchemically assisted thermal desorption (CATD) capability to control thefragmentation pathway during the temperature programmed desorption. CATDdesorbs explosives under controlled chemical environments. During thedesorption process, unstable explosives undergo known decompositionpaths, resulting in predictable and detectable fragment ions in theHTCIMS. CATD can greatly enhance system sensitivity and specificity ofperoxide detection, especially for HMTD that is known for rapiddecomposition during the thermal desorption process.

In another aspect of the invention, the capability of the HTTD will befurther improved by allowing modernized ionization methods to beutilized. With electrospray ionization, black powers and other inorganicexplosives can be reliably detected. The invention describes a combinedthermal desorber and electrospray unit without additional mechanicalcomponents and pumps. The new HTTD has a multi-function sampleintroduction apparatus that can also accommodate multiple sampleintroduction ports for introducing samples in vapor, liquid and solidphases. The liquid injection port can be used to analyze unknown liquidswith minimal sample preparation. In addition, the compatibility of othernew ionization methods, such as DESI and DART may be used.

In another set of embodiments, the HTTD will be developed as aninterface to MS. With versatile sample introduction and high throughputperformance, the HTTD as a front end will eliminate many problems whenconverting laboratory MS systems to field chemical detectionapplications. One of the major issues for tandem IMS-MS is the iontransportation efficiency between high pressure IMS and high vacuum MS.HTTD-MS will address this issue with three electric field zoneextraction. The integrated HTTD-MS system not only has the potential forbeing used as an advance trace detection system, but also can be becomethe benchmark used to evaluate the performance of all other ETDs used inexplosive detection applications.

In yet another set of embodiments, a multi-function sample introductionapparatus can be used for: thermal desorption of solid samples on asubstrate or from a removable sample holder, electrospraying liquidsamples from a liquid inlet, and electrospraying a sample from aremovable sample holder.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

The present invention relates to ion mobility spectrometers and tomethods of operating ion mobility spectrometers. In one embodiment, theion mobility spectrometer of the present invention uses a simplified ionmobility spectrometer design having helical resistive material, such ashelical resistive wire. The helical resistive wire forms substantiallyconstant electric fields that guide ion movements. The drift tube forion mobility spectrometers described herein is constructed with anon-conductive frame, resistance wires, an ion gate assembly, aprotective tube, flow handling components, and an ion detector assembly.In some embodiments, single or plural resistance wires are wrapped onthe non-conductive frame to form coils in various shapes, such as round,oval, square, rectangular, or other polygons shapes. The coil generatesan even and continuous electric field that guides ions drift through theion mobility spectrometer.

In addition to forming the electric field, the helical resistive coilcan increase the temperature of the drift tube and any gases flowingthrough the drift tube. In some embodiments of the ion mobilityspectrometer of the present invention, the drift tube temperature iscontrolled by using the helical resistive coil and a heating elementthat preheats the drift gas to the designed temperature. The drift gasis delivered directly inside the coil and pumped away from the gasoutlet on the protective housing. This configuration provides a robustion mobility spectrometer that is simple to build with lower thermalmass along the ion and drift gas path, thus allowing rapid temperaturemodulation, which is required by some applications.

One feature of the present invention is that the drift tube designdescribed herein enables the ion mobility spectrometer to be built witha lower weight, lower power consumption, lower manufacturing cost, andfree of sealants that may out gas. In addition, the drift tube can beisolated from ambient environment using vacuum sealing methods that cansustain pressure levels greater than atmospheric pressure.

In addition, the ion mobility spectrometer configuration describedherein provides a means to rapidly change pressure inside of the drifttube during the ion mobility measurement. The resistance coil baseddrift tube configuration allows operating time-of-flight type IMS underhigh electric field conditions. Measuring ion mobilities of the sameionic species under both high and low field conditions (E/p ratio)provide additional information for ion identification. Unresolved ionmobility peaks under low field conditions may be separated andidentified under high field conditions. Methods of sequentiallymeasuring ion mobilities under different E/p ratio according to thepresent invention allows correlating low field and high field mobilitiesfor comprehensive ion identification.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects, embodiments, and features of theinventions can be more fully understood from the following descriptionin conjunction with the accompanying drawings. In the drawings likereference characters generally refer to like features and structuralelements throughout the various figures. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the inventions.

FIG. 1 schematically shows one example of a low thermal mass IMS using aresistance coil structure;

FIG. 2 schematically shows an example of low thermal mass component forIMS using a resistive material affixed on a dielectric substrate;

FIG. 3 schematically shows a IMS using a metalized dielectric structureand details of the leading electrical contacts in the IMS construction;

FIG. 4 schematically shows a IMS using a metalized dielectric structurethat consists of multiple dielectric substrate components; in particularthe metalized dielectric substrates are substantially flat;

FIG. 5 schematically shows a construction of a Bradbury-Nielsen ion gateusing metalized dielectric rings and parallel wires;

FIG. 6 schematically shows a stack ring design using high thermalconductive electrodes (metal) and dielectric spacers that allow rapidheating and cooling of the apparatus using a heat pump;

FIG. 7 schematically shows a chemical assistant thermal desorptionapparatus that chemically modifies the environment during thermaldesorption of samples on a swab and/or a preconcentrator.

FIG. 8 schematically shows a multi-function sample introductionapparatus;

FIG. 9A-C are drawings that show the removable sample holder (9A showsthe sample holder open with a sample swab inside, 9B shows the closedsample holder, and 9C shows the closed sample holder inside themulti-function sample introduction apparatus;

FIG. 10 schematically shows details of the interface between aorthogonal TOFMS and an IMS;

FIG. 11 schematically shows the mechanism of extracting ions in atransverse direction from the extraction zone into a vacuum inlet;

FIG. 12 schematically shows examples of drift ring or guard ringconfigurations for the extraction zone;

FIG. 13 schematically shows the mechanism of extracting ions in axialdirection from the extraction zone into a vacuum inlet;

FIG. 14 schematically shows an example of IMS-MS interface; particularlyan IMS is interfaced to an orthogonal TOFMS where ions are extractedfrom IMS in the transverse direction of their drift axis.Multi-dimensional IMS can be operated under different pressureconditions before mass analysis;

FIG. 15 schematically shows a preferred embodiment of the IMS andorthogonal TOFMS interface where the drift axis is parallel to theflight axis in the TOFMS. A vacuum inlet with an array of pinholes isshown to demonstrate effective sampling of a portion of mobilityseparated ions in transverse direction.

FIG. 16 illustrates a schematic diagram of an embodiment of the ionmobility spectrometer of the present invention.

FIG. 17 illustrates an alternative embodiment of the drift tube of thepresent invention.

FIG. 18 illustrates a rectangular resistance coil built from a singleresistance wire with four-rod supporting frame.

FIG. 19 illustrates a round resistance coil built from four resistancewires on a supporting frame.

FIGS. 20A and 20B illustrate cross-sectional views of the four-wirecoil. FIG. 20A depicts a radial cross section of the four-wire coil.FIG. 20B depicts a local axial cross section view of the four-wire coil.

FIGS. 21A and 21B illustrate cross-sectional views of an inner and outerconcentric coils and detector matrix. FIG. 21A depicts a local axialcross section of the concentric coils and detector matrix. FIG. 21Bdepicts a radial cross section of the detector matrix with multipleFaraday plates that is used to detect ions in an ion mobilityspectrometer according to the present invention.

FIG. 22 shows ion source outlet configurations of the ion mobilityspectrometer according to the present invention.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

As used herein, the term “analytical instrument” generally refers to ionmobility based spectrometer, MS, and any other instruments that have thesame or similar functions.

Unless otherwise specified in this document the term “ion mobility basedspectrometer” is intended to mean any device that separates ions basedon their ion mobilities or mobility differences under the same ordifferent physical and chemical conditions and detecting ions after theseparation process. Many embodiments herein use the time of flight typeIMS, although many features of other kinds of IMS, such as differentialmobility spectrometer and field asymmetric ion mobility spectrometer areincluded. Unless otherwise specified, the term ion mobility spectrometeror IMS is used interchangeable with the term ion mobility basedspectrometer defined above.

Unless otherwise specified in this document the term “mass spectrometer”or MS is intended to mean any device or instrument that measures themass to charge ratio of a chemical/biological compounds that have beenconverted to an ion or stores ions with the intention to determine themass to charge ratio at a later time. Examples of MS include, but arenot limited to: an ion trap mass spectrometer (ITMS), a time of flightmass spectrometer (TOFMS), and MS with one or more quadrupole massfilters.

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases.

The present invention generally relates to systems and methods ofanalyzing samples using a chemical and/or biological analyticalinstrument, in particular this invention addresses current issues ofexplosive detection by developing a comprehensive detection system basedon common core technologies: a high thermal conductivity material and/ora low thermal mass construction, a novel sample introduction system, anda novel instrument interface system. All of these novel features ethertogether or used separately improves the currently used technology. Thesubject matter of the present invention involves, in some cases,interrelated products, alternative solutions to a particular problem,and/or a plurality of different uses of one or more systems and/orarticles.

In one set of embodiments of the invention, a HTTD is based on highthermal conductivity ion mobility spectrometers (HTCIMS). The uniqueconfiguration of the HTCIMS allows rapid change of detector temperaturethus enabling time-temperature desorption methods and TRUE temperatureramping in the trace detection process. True temperature ramping enableshigher sensitivity and selectivity for peroxides detection, as well asother thermally labile explosives. The low thermal mass construction ofthe HTCIMS will also allow rapid system clean up in seconds, whicheliminates system down time in high throughput trace detectionapplications. In addition, the low thermal mass construction allows alower overall power consumption system that is useful for portabledetection applications.

In another set of embodiments, the configuration of the HTCIMS, avariety of ionization methods, including but not limited to radioactiveionization, corona discharge, electrospray, desorption electrospray,DART, secondary electrospray ionization, photo ionization and etc., willbe used to ionize targeted chemicals. The ionization source structurewill also be designed to accommodate multiple ionization methods.

In some embodiments, the low thermal mass constructed analyticalinstrument 100 is shown in FIG. 1. The drift tube and reaction region ismade from a wrapped resistance coil 105 that allows rapid temperaturegradients, either heating and/or cooling. The other components shown inFIG. 1 include; a thermal desorber 110, an ion gate 115, a Faraday ioncollector 120, and a protective tube 125.

The resistance coil ion mobility based spectrometer (RCIMS) uses helicalresistive material to form constant electric fields that are used toguide ion movements in an IMS. This drift tube for IMS is constructedwith a non-conductive frame, continuous resistance wires, an ion gateassembly, a protective tube, flow handling components, an ion detectorassembly, and other components. The resistance wires are wrapped on thenon-conductive frame form coils in a round (or polygon) shape. The coilgenerates an even and continuous electric field that guides ion driftthrough the IMS. The resistance wires are not only used to form theelectric field, they also function as the heating element to heat up thedrift tube. The IMS design controls drift tube temperature using theresistive coil to maintain drift gas temperature; a separate heatingelement is used to preheat the drift gas before entering the driftregion. The drift gas is delivered directly inside the coil and pumpedaway from the gas exit on the protective housing. This configurationprovides a robust IMS that is simple to build with extremely low thermalmass along the ion and drift gas path, thus allowing rapid temperaturechanges. In summary, the drift tube design enables the IMS to be buildwith lower weight, lower power consumption, lower manufacturing cost,and is completely free of sealants that may out gas causingmanufacturing problems for conventional spectrometers. An exampleconfiguration of a RCIMS: using 51 gauge Alloy COJ to construct a drifttube of 1.5 inch in diameter and 4 inch long, the total resistance is1.4 Mohm; power consumption of 4.7 W at a drift field strength of 250V/cm.

The RCIMS can be operated in either positive or negative ion mode, or arapid switching mode (note that the basic concept of polarity switchinghas no patent infringement issue). With much lower total resistance, thedrift field can be established much faster compared to common drift ringdesigns. The linked desorber-detector temperature ramping is achieved bycontinuously increasing voltages on the coil over ionization andreaction regions. In addition, if the drift voltage is also ramped inthe same fashion, additional information could be generated by analyzingkinetics of ion decomposition reactions and transportation properties togain higher specificity for explosives detection. At the end of eachtemperature ramping program, the spectrometer can be completely cleanedup by increasing the voltage across the spectrometer: a) all residueions in the drift tube will be accelerated and neutralized on thecollector; b) the coil temperature may increase to 500-600° C., thus allchemical residues on the wall of the drift tube will be evaporated intopurge flow or decomposed (note the Alloy COJ has a melting point of1200° C.).

In addition, with electrical current passing through the resistancewires, the coil can create a magnetic field inside the spectrometer.This magnetic field is used to effect ion movements in the RCIMS. Withthe effects of ion focusing and de-focusing, two-dimensional separationcan be achieved by adjusting the electric and magnetic field conditionsinside the drift tube. In the RCIMS design, the ions can be pushed outof the ionization source through a much smaller opening. After enteringthe drift region, the ions will not only drift down the drift tube underinfluence of the electric field, but also move in a circular motionbecause of the circular component of the electric field generated by theresistance coil. When the ions cut through the magnetic field, they arepushed toward the coil. The strength of the force is related to thespeed of the ions which is determined by their ion mobilities.Therefore, ions with different mobility are detected at differentlocations on the Faraday plate. A Faraday plate that consists ofmultiple concentric rings can be used for obtaining the two-dimensionalseparation data. The 2D detection approach can improve the detectorspecificity and reduce false alarm rates.

In one set of embodiments, the low thermal mass structure is a resistivematerial 201 affixed on a non-conductive (dielectric) wall 205 as shownin FIG. 2. The term affixed should be understood to mean deposited onthe surface though process, such screen printing or thin filmdeposition. The wall could be made of non-conductive material including,but not limited to, ceramic, fused silica, quartz. In particularly,highly thermal conductive and dielectric material including, but limitedto, beryllium oxide (BeO) and aluminium nitride (AlN) represents thebest choice. However, other materials, such as alumina (Al₂O₃) or anyother kind of ceramics has suitable electrical properties and mechanicalstructures can also be used for the analytical instrument construction.In a variety of embodiments, the resistive material can be arranged in,but not limited to, a serpentine line (as illustrated in FIG. 2),multiple lines that are substantially parallel straight or curved fromthe first end 200 to the second end 202 of the wall. The analyticalinstrument can be assembled using one or multiple pieces of wallstructure. The wall could be in any shape that is suitable forconstructing the analytical instrument including, but limited to, a flatplate, a curved plate, a round tube, a half round tube, a rectangulartube.

Yet another aspect of the present invention is the IMS using a metalizeddielectric structure to create necessary electrode layout for generatingelectric field in the IMS. A metalized dielectric tube is shown in FIG.3. To realize the design as shown in this figure, the dielectric tube301 is first machined for between inner and outer surface quality; arrayof holes for the leading electrical contacts are also prepared 315; andthen, the entire inner surface is coated with single or multiple layerto metallization materials. The metallization process is commonlyfinished with a thin layer of nickel, gold or other inert metal forenhanced chemical resistivity. The metalized inner wall of the tube isthen machined into rings by removing a narrow gap of the metal layer (asshown in FIG. 3). The metalized rings on the inner wall 303 of the tubeare connected to the power supply via array of electrical contact wires305 through the holes on the wall. An ion gate 311 is also shown in FIG.3. A heater 307 and a heat sink component 309 for cooling are tightlymounted on the outer wall of the dielectric tube. As high thermalconductivity ceramic will be used for this contraction, the heating andcooling process is expected to be accomplished within seconds. Withoutpursuing the highest heating and cooling rate, the ceramic material canbe 92 to 99.9% alumina, Al₂O₃, or any other kind of ceramic that hassuitable electrical and mechanical properties. For optimized thermalconductivity, aluminum nitride (AlN) can be used as the base ceramictube for the drift tube structure. Beyond the examples given above,other dielectrics with high thermal conductivity and the properdielectric constants could also be used for the IMS drift tubeconstruction.

In one set of embodiments, the IMS using a metalized surface on asubstantially flat dielectric material, such as ceramic, but not limitedto this material is shown in FIG. 4. In addition, the dielectricmaterial (substrate) does not necessarily need to be flat, but caninclude a curved shape. A thin layer of nickel, gold or other inertmetal 404 for enhanced chemical resistivity is formed directly on thesubstrate 402 using an additive method such as screen printing and thinfilm deposition to each inner wall. Conductive leading contacts 408 areeither extensions of metalized pads or bonded lead wires. The flatplates can be assembled into an enclosed chamber for use in an IMSspectrometer. The assembled shape of the metalized flat plates shown inFIG. 4 is rectangular, although the metalized flat plates can beassembled into any useful shape, in particular, square. The assembled 4plates can have metalized pads that are: individual, partially connectedforming a partial ring structure, and interconnected to each otherforming a full ring structure. In the case of the interconnected orpartially connected metalized pads, the number of lead contacts or wiresused may be less then when employing individual metalized pads. Aheating element or heating elements can be arranged surrounding theenclosed chamber or mounted on one or more plate(s) in case high thermalconductivity materials used for the construction of the entire plate canserve as a heater for the enclosed chamber. Reduced thermal mass of thisdevice can be achieved by choosing high thermal conductivity substrateand reducing physical dimension of components and overall device.

In one embodiment, components of an IMS using a metalized ceramicmaterial is shown in FIG. 5. FIG. 5 shows a unique construction methodof a Bradbury-Nielsen ion gate. It is built with a frame ring, a tensionring 502 and parallel wires 505 that are pre-winded on a metal frame.One or the rings, either the frame ring or the tension ring is metalized515 with a pattern 510 that connects every other wire to each other. Inone embodiment, the frame ring has metalized contacts 507 that are 1 mmapart (center to center). During the ion gate construction, the parallelwires are lined up with these contacts and form a firm contact while thetension ring is pushed down into the frame ring. As the wire is selectedto match the thermal expansion of the frame ring and tension ring, thewires can be maintained parallel while the IMS is operated underdifferent temperature conditions. The gate control voltage(s) areapplied to the wires by attaching an electrical lead to the contactpoint that is on the outside of the frame ring. Not only for metalizedceramic tube IMS design, the Bradbury-Nielsen ion gate can be used forother analytical instruments.

In another embodiment, the invention using the HTCIMS has a stack ringdesign IMS; this device is designed and constructed using high thermalconductive electrodes (metal or metal coated components) and insulationmaterials (dielectric) for rapid heating and cooling methods. A heatsink with cooling means will be used to rapidly pump away the excessiveheat after each heating cycle. FIG. 6 shows one embodiment that uses aheating belt 603 that is mounted on a dielectric structure 605 and aforced air heat pump 607 to rapidly heat and cool the device. A heatpump as used herein is a device to add or remove heat from analyticalinstrument. Unrelated to the specific example shown in this figure, theheat pump can be used on any IMS device and/or analytical instrument.The heat can also be added or removed from a device via a media, such asgas or liquid. An ion detector 615 and an ionization source 620 arepictured, although both of these elements of the instrument could beused externally. A drift gas preheating element (not shown in thefigure) is also used to work cooperatively with the drift tubetemperature control components described above. Instead of traditionalstainless steel guard rings used in many previous art IMS, the HTCIMSuses high thermal conductivity metals and/or alloys for the guard ringconstruction 610, i.e. gold coated aluminum rings, but not limited tothese. The spacer between guard rings 612 are also made of high thermalconductivity materials, i.e. AlN, but not limited to this. With theHTCIMS, the heating and/or cooling of the device from 50 to 350° C. canbe achieved within several seconds. In trace detection applications, therapid heating and cooling is used to perform synchronized thermaldesorber-IMS temperature ramping, on-the-fly desorber and IMS clean up,declustering ions in unwanted form during IMS measurements and study ionchemistry in the drift tube. One method for operating the low thermalmass IMS comprises: rapidly adjusting an IMS temperature to the firststarting operating temperature and then ramping the temperature to theending operating temperature at a designed rate using the heat pump.This method of ramping the temperature can be done while, before, orafter obtaining ion mobility spectra. This method can also include:ramping temperature of a thermal desorber that is in fluid communicationwith a sample inlet of the IMS wherein the design rate of the IMStemperature ramping is substantially equal to or higher than thedesorber temperature ramping rate. This method of temperature rampingcan also be used for cleaning the IMS in-between sample runs.

In another set of embodiments of the invention, FIG. 7 shows theapparatus of the HTCIMS with a thermal desorber 702 for swiped (swabbedusing dry or wet swabs) sample 703 and a preconcentrator 704 for vaporsand particles collected from air; this preconcentrator is particularuseful for peroxide detection from the gas phase. The home madeexplosive (HME) vapor preconcentrator is made from plural layer ofcoils. The coil is made of resistance alloy. The pitch size of the coilis made to precisely trap/filter out certain size of the particlesduring preconcentration. Multiple coils could be made with differentpitch sizes to achieve multiple step filtrations. As shown in FIG. 7,When the sample flow “710” enters the preconcentrator chamber, it passthrough the coils (only single layer of coil is shown) and then pumpedaway with flow “715”. The particles of different sizes are trapped ondifferent layer of coils. The vapor sample can be trapped on any coilswhen interacted with the coil surface. They could be trapped without anyaffinitive coating as the preconcentrator is at related low temperature.During the sample preconcentration stage of operation, valve V1 isclosed, V2 and V3 are open to allow flow to pass design direction. Inaddition, the affinity layer coating material generally has higherelectrical resistance compared to the coil material itself. Thus it canfunction as insulating layer when electrical current is passing throughthe coil for flash heating. Different coils or different section of thecoil can be coated with different material to trap chemicals ofdifferent classes.

During the desorption process, a local chemical environment is createdto assist sample desorption/evaporation process. The function of thesechemicals is either to directly react with the trapped samples andconvert them into IMS detectable form, or to control their fragmentationpath way at elevated temperature. To introduce additional chemical tointo the preconcentrator, valve “V2 and V3” are closed, V1 is open, thusGas flow “720” that pass through a chemical chamber 725 is introduced tothe preconcentration chamber during the desorption process. During thedesorption process, the coils are flash heated with controlledtemperature ramping speed to evaporate the trapped chemicals. If thechemicals are not necessary, the desorption flow can be redirected byclosing V1 and open V3. There are many thermal labile explosives thatdecompose before being evaporated, the CATD can be used to create knownfragments and subsequentially detected by RCIMS. Similarly, CATDapproach can also be used during the desorption of sample on a swipe(substrate) (in this case V1 & V2 are closed and V3 & V4 is open). Theairflow 730 will bring desorbed sample into the resistive coilspectrometer 755, the ionization source 750, and both drift flow 740 andsample flow 730 will be purged via V3 through flow 745. The CATD canpotentially be a great advantage when used HTTD for peroxide detection.For example, Hexamethylene Triperoside Diamine (HMTD) does not havesensitive response IMS based systems because of the thermaldecomposition, however, if the explosive is desorbed in the modifiedchemical environment that is doped with acidic vapor, a decompositionproduct can be predicted. In this specific case, the product isperoxy-bis-methanol [Jounal; Legler; CHBEAM; Chem. Ber.; 18; 1885; 3344]that could be sensitively detected by HTTD in the negative ion mode.CATD can not only being used for peroxides detection, but also improvedetection of other thermal labile common explosives or taggants.

In yet another set of embodiments of the invention, the sampleintroduction system is threefold; to add an electrospray method that iscompatible with current sampling techniques, add additional sampleintroduction ports that can be used to directly introduce liquidsamples, and combine with other ionization methods, such as DESI andDART for HTTD. The compatible electrospray ionization add-on for HTTDwill address one of the major shortcomings of IMS based trace detectors,i.e. detection of low explosives, such as black powers, and othernonvolatile explosives, such as inorganic sodium chlorate and ammoniumperchlorate. In addition, with the importance and recent interests intouchless sampling, interfacing the HTTD with DESI and/or DARTionization methods may enable the HTTD to collect samples remotely. Moreimportantly, if the ions created by these ionization methods can beeffectively introduced into the HTCIMS, then the HTCIMS can be used toisolate the MS system from contaminants that are desorbed from thesampling surface. As most mass spectrometric system are operated at roomtemperature, desorbed neutral explosive samples and contaminates caneasily accumulated at the inlet area other components that are exposed.System clean up and false alarms are anticipated under field operatingconditions, especially since many of these ionization methods requirehigh sample flow rate for the desorption ionization.

In some embodiments, a wet sampling scheme, e.g., electrosprayionization can be used to process the wet samples by directly sprayingcollected sample into the ionization chamber. One implementation of thismethod includes having the wet samples put into a removable sampleholder, which has an electrospray needle and electrodes where anelectrospray voltage can be applied. As the sample is sealed inside theholder, pressure is applied to the holder/soaked sample substrate eitherdirectly or indirectly, and the solvents and dissolved sample reach theelectrospray needle, and are electrosprayed to form highly chargeddroplets. The electrospray sample ions can be guided into the ionizationchamber for analysis. The combination of wet sampling and directelectrospray ionization for the instrument can provide, for example,detection capabilities for both inorganic and organic explosives andother chemicals of interest.

Unless otherwise specified in this document the term “particle” isintended to mean chemical and/or biological single or plurality of atom,molecule, large or macro molecule, nanoparticle, or other matters thatare; solid, liquid, crystal, charged species, vapor, droplets, anaerosol, gas, supercritical fluid and/or other fluidic materials or anyother medium in which specific molecules of interest may bedeposited/applied to a sampling substrate.

Sampling particles from a desired target utilizing a sampling substrateor swab can be accomplished in many ways, including but not limited to:physically touching (wiping) a sampling substrate across a surface andthen inserting the sampling substrate in a detector or a removablesample holder for analysis and/or collecting the particle on a samplingsubstrate without contacting the surface followed by directly insertingthe sampling substrate into the detector or removable sample holder.

In a variety of embodiments, FIG. 8 shows the multi-function sampleintroduction apparatus 801. Utilizing the current sampling technique,i.e. swipe (swabbing) and particle desorption operation, the samplingsubstrate can be inserted into a sample loading port between the shapedheating plate 803 (thermal desorber) and sample inlet screen 805, in thelocation of the illustrated removable sample holder 809. As the samplesare heated up with the temperature program, they are vaporized andtransferred into the ionization chamber of the instrument by way of anopening and/or interface that has a gas outlet. The vaporized sample isionized by an ionization source 807, such as a corona discharge source,but not limited to this source. The ionization chamber has an openingthat accepts a sample in neutral and/or ionic form. For liquid sampleintroduction, a liquid inlet 808 is also included in the apparatus whichcan electrospray the liquid sample by applying a voltage. The removablesample holder 809 that that is illustrated in FIG. 8, containing aplurality of electrospray nozzles 811 can also be inserted into themulti-function sample introduction apparatus 801. With the electrospraycapability, unknown liquids can be placed on the sample substrate andelectrosprayed into the spectrometer. The multi-function sampleintroduction apparatus 801 can be interfaced to a variety ofinstruments, such as a MS, a ion mobility based spectrometer, inparticular a high thermal conductivity IMS, but not necessarily limitedto these.

One embodiment of the invention relates to transferring the samplingsubstrate to a removable sample holder prior to analysis. The removablesample holder comprises: a substantially sealed inner chamber, at leastone opening for releasing a sample to a spectrometer, and at least oneopening to receive the sample. In addition, the removable sample holdermay include a single or plurality of electrospray nozzles, an electricalcontact, and/or a porous material, such as foam, sponge, zeolite,membrane, metallic foam, but not limited to these that a applied solventcan flow. The removable sample holder body can be made from a number ofmaterials that are inert from outgasing and/or experience chemicalchanges in their composition while being exposed to any solvents ormixtures of solvents, in addition the removable sample holder can bemade from a material that can withstand rapid heating from low to hightemperatures. The removable sample holder body may include anidentification marking, such as a bar code or rf tag, but notnecessarily limited to these. The solvents or mixtures of solvents thatmay be applied to the porous material may include; water, acetonitrile,alcohols, in particular, methanol and ethanol, hydrocarbons, inparticular, hexane and pentane, halogenated, in particular methylenechoride and chloroform, ketones, in particular acetone, but not limitedto these; any suitable solvent or mixture of solvents that can dissolvethe sample for use in a electrospray process.

In some embodiments, where the removable sample holder will be used formultiple sample introductions, the removable sample holder can bedelivered in a sealed bag. Removal of the bag or solvent sealing stripmakes the removable sample holder ready for use. The removable sampleholder can be re-used for multiple sampling substrates (swabs). Onesample introduction method would comprise: loading a known amount ofsample into the removable sample holder, then inserting a removablesample holder into a sample loading port, and vaporizing some sampleunder a controlled temperature and/or temperature gradient into theionization chamber. Another substrate sampling introduction methodcomprises: swabbing a sample with a wet or dry swab, loading the sampleinto a removable sample holder, dissolving the un-dissolved sample, andthen electrospraying the dissolved sample into a analytical instrument.

In a non limiting example of the removable sample holder being used forelectrospray ionization, the sample substrate 900 is placed in an openremovable sample holder 902 within which a porous material 903 is soakedwith solvent or solvent mixture for electrospraying (FIG. 9A); when theremovable sample holder is closed 904, the knife edge ring 905 will pushdown into the lower body 907 and form a seal around the electrospraynozzles thus forming a sealed inner chamber (FIG. 9B); as the sampleholder is inserted between the shaped heating plate (at roomtemperature) and the sample inlet screen, the electrospray nozzles willbe set at a higher voltage against the sample inlet screen. Meanwhilethe shaped heating plate 910 will push into the porous material andcreate a higher pressure to start the electrospray (FIG. 9C). Theremovable sample holder may include an electrical contact 901incorporated into the body and may also include at least one deformablesurface that allows for increasing the pressure in the sealed innerchamber.

In one embodiment, the inner surface of the electrospray nozzle will betreated to be hydrophilic to the selected solvent and hydrophobic forthe area surrounding the nozzle. When the holder is closed, the solventwill soak through the sample substrate and the dissolved samples will beaccumulated in the electrospray nozzle with a local high concentration.Pulsed electrospray operation and positive and negative spray operationwill be used to analyze both positive and negative ions.

A variety of materials, according to certain aspects of the invention,can be used to form any of the above-described components of the systemsand devices of the invention. In some cases, the various materialsselected lend themselves to various methods. For example, variouscomponents of the invention can be formed from solid materials that areinert. These inert materials should not outgas at elevated temperaturesand/or experience chemical changes in their composition while beingexposed to solvents, solvent mixtures, and/or heat. In one embodiment,the sampling substrate is made of a porous material such as cellulose,fabric, glass fiber and/or a fine wire mesh, multilayer diffusion bondedmetal screens but not limited to only these materials. The screens canbe made of, but not limited to, stainless steel, bronze, Monel, andother metal alloys. The opening of the screen may be in the range fromsub-microns to hundreds of microns. The sampling substrate can be anysize or shape that would be suitable for use in the described apparatus.

In another embodiment, the above-described porous material used for thesampling substrate can be chemically treated to assist in particlesampling, in particular for vapor sampling, the sample substrate mayalso be coated with a layer of affinitive material, such as modifiedPDMS used for SPME. Possible coating material may also include afunctionalized surface, such as sol-gel. In addition to and includingsampling vapors, the sampling substrate material may have chemicalfunctionality covalently linked through the matrix of the material.These functional groups will assist in collecting the particles on thesampling substrate. For example, certain explosive materials areinherently sticky, such as C-4 (a RDX based explosive), and Deltasheet(PETN based explosive). Due to their makeup, these explosive moleculesare generally greasy substances and are hydrophobic. Particles which arenot explosive molecules can also be hard to remove from the surface andthe methods disclosed below can be used not only for explosivemolecules, but for particles in general. A non-limiting example of suchfunctional groups are hydrophobic groups, such as an alkane, alkene,benzene derivative, haloalkane, but not limited to theses, that arechemically linked through a covalent bond to a cellulose matrix.

In alternative embodiments of the invention, the HTTD is used as sampleintroduction/pre-separation method for MS. Even though the HTTD has highresolution and is suitable for rapid screening of trace chemicals, thecombination of HTTD and MS can provide addition technical merits. MSsystems have greater resolution and the potential to reduce falsealarm/identification rates for trace chemical detection applications. Asmost mass spectrometric instruments are configured for laboratory use,advanced sampling methods are required field trace detectionapplications. The HTTD can be interfaced to a MS as an integrated IMS-MSsystem. Compared to other types of MS, TOFMS may the advantage of higherresolution and rapid data acquisition. However, it also requires highervacuum for operation, and it has been a major challenge to interface anatmospheric pressure IMS to a TOFMS because of the greater pressuredifference. FIG. 10 shows the concept of interfacing the HTTD to theorthogonal interface 1005 of a TOFMS. In a variety of embodiments, thefigure shows the HTTD 1001 is interfaced to a TOFMS (not shown) Themobility separated ions are extracted into the MS under vacuum throughan interface assembly 1010 that may consist of, but not limited to, apin-hole opening, single/multiple tube structure, or a slit opening incombination with skimmers and/or other ion optics commonly used forstate of art MS. The ion extraction zone 1006 at the end of the HTTD andthe interface assembly 1010 to MS are described in details in latersections. The integrated HTTD-MS detection system has improvedselectivity and a versatile sample introduction apparatus as describedin previously.

To resolve the ion transportation issues at IMS-MS interfaces, severalion extraction methods in front of MS interface are described in thisinvention. In a variety of embodiments, a novel multiple field zone ionextraction mechanism is described to extract ions in front of the vacuuminlet into the MS under vacuum conditions. FIG. 11 shows a non-limitingexample of extracting mobility separated ions into the MS. When a groupof mobility separated ions 1101 travels into the ion extraction zone1103 through a grid 1116 that serve as a separator of the ion extractionzone and ion drift region, ions are kicked out from high field zone 1105to a low field zone 1107 in front of the MS interface. In this low fieldzone, the “ion plug” is compressed in the direction that isperpendicular to its drift direction 1109 into a narrow band 1110. Onthe other hand, a high field zone 1112 is created by adding substantialvoltage difference on each side of vacuum inlet tube 1115. Theconfiguration of this inlet tube can be similar to a time of flight typeIMS but with a small internal diameter. In particularly, the inlet tubecan be made of a resistive glass tube. At the boundary area between highfield zone 1112 and the low field zone 1107, an ion focusing effect canbe achieved to extract ions from a larger area into the MS. As the ionsare kicked out into this area, they can be transported into the MS withhigher ion population. In a practical application, the high voltage ionkick out pulse is on for several microseconds. The ion extraction can beperformed on the entire ion mobility spectrum or can selectively extractions with mobilities of interest into the MS. As chemicals have alreadybeen ionized and separated in the HTTD, only chemicals that have thesame ion mobility will be introduced into the MS during each kick out.

As discussed above, the method of mass analyzing mobility separated ionsmay involve generating ions in front of a IMS, separating ions in theIMS and transporting ions in the front of a vacuum inlet, collecting asection of mobility separated ions into the vacuum inlet in thedirection that is perpendicular ion drift direction; and measuring massto charge ratio in a MS. The method may also involve transporting ionsinto an ion extraction zone; and then compressing ions by applying apulse of high electric field in the ion extraction zone, the ions arepushed into a low field zone in front of vacuum inlet. The ions arefurther transported and/or focused into the vacuum with assistance of alocal high field inside the inlet and a gas flow. Alternatively, amethod of introducing ions into a vacuum may involve transporting ionsfrom a high pressure condition in to an ion extraction zone, and thencompressing ions by applying a pulse of high electric field in ionextraction zone and push them into a low field zone in front of vacuuminlet; and further extracting ions into the vacuum inlet with anotherhigh electric field.

FIG. 12 shows examples of possible embodiments of drift ring or ionguide configuration for ion extraction zone. As shown in FIG. 12, manypossible configurations can be used and the invention is not limited toa round ring shape structure. The electrodes are arranged to provideoptimal electric field for the ion extraction and the maximum efficientfor ion extraction.

In FIG. 13, the mobility separated ions 1301 are compressed/condensed1303 by the kick out voltage temporarily applied in the first high fieldzone 1305 that is defined by the field separator grid 1307 and anoptional grid can as be placed between the high field (extraction) zonethe vacuum inlet. The ion compression is in the direction that is inline with their drift direction. Compared to the method described inFIG. 11, the total amount of available ions can be less. The transversefield ion extraction can theoretically improve system sensitivity. Analternative embodiment of using transverse field ion extraction at theIMS-MS interface may not involve ion compression described in FIG. 11.Simply extract mobility separated ions into a MS in the direction thatis perpendicular to their drift direction can provide better IMS-MSsystem sensitivity compared to inline IMS-MS interface that has bedemonstrated in prior arts.

FIG. 14 shows the concept of one of the embodiments for interfacing anIMS to a TOFMS. An ion source 1402 is used for generating ions underambient pressure conditions; An IMS 1403 having an inlet 1404 at firstend accepting ion from the ionization source; As the ions are broughtinto the IMS, they are subsequently separated based on ion mobilityalong the drift axis; the ions enter ion extraction zone through a fieldseparating grid 1407; the ion extraction zone locating in front of thevacuum inlet 1401 is designed to assist extracting ions from the IMSinto the vacuum inlet in the direction that is substantiallyperpendicular to the ion drift axis; ions are kicked out from the ionextraction zone into a the vacuum inlet; the drift rings (or ion guideor guard rings) are segmented elements 1416 (View B) as described alsoin FIG. 12, where an extraction electric field can be created byapplying a designed voltage on each element. During the ion kick outprocess, the normal ion drift electric field is temporarily converted toa strong electric field that is perpendicular to the drift axis, thusions in the extraction zone are forced to move in the direction that isperpendicular to the original drift axis. The temporary ion extractionfield is relatively short in time compared to ion drift time, thus ionsoutside the ion extraction zone can maintain their drift motion whileions in the extraction zone are forced toward the vacuum inlet. The ionextraction field is arranged to avoid mixing mobility separated ionsduring the extraction. As shown in the figure, the interface 1401 doesnot necessarily need to be a round orifice, pin-hole, or tubing; itcould also be an array of pin-holes or an slit, or any other shape thatallow multiple mobility separated ions entering the MS at same time. Thefigure shows an IMS-TOFMS interface; however, the interface could beused with other types of MS as well, such as, a microarray ion trap massspectrometer, linear ion trap mass spectrometer, etc. Depending on theshape of the vacuum inlet, a section of mobility separated ion pocketsare sampled into the vacuum inlet in the direction that is perpendicularto the ion drift direction. In a variety of embodiments, FIG. 14 shows anon-limiting example of using orthogonal TOFMS to measure mass to chargeratio of mobility separated ions. As ions are leaving IMS and enter theorthogonal interface 1408 (view B), they are directed into the ionaccelerator 1411 by surrounding electric field and ion propeller 1410,if necessary; the ions fly through accelerator, field free region,reflectron 1412, and then to ion detector 1414. Note that instruments,such as MS and IMS, illustrated in this specification does representaccurate/complete configurations, they are used as non-limiting examplesto show the concept of this invention; state of the art instruments,e.g. TOFMS, should be used in practice.

In addition, a multidimensional IMS can provide multiple step mobilityseparation prior to mass separation. As a multiple drift tube is used,each dimension of IMS drift tube may be operated under differentpressure conditions. In FIG. 14, if the ionization source 1402 isreplaced with a drift tube and the drift tube is operated under higherpressure conditions, the drift tube 1403 shown in this figure can beoperated under a different pressure. With the first dimension drift tubeat ambient pressure and second drift tube at medium pressure, e.g. frommTorr to 100 s Ton, MS interfaced to second dimension drift tube mayhave a bigger opening, because of the reduced pressure differencebetween the second dimension drift tube and vacuum chamber for MS, theion transfer efficiency can be improved. In summary, the apparatus ofmass analyzing mobility separated ions using a first IMS having an inletaccepting ions from an ion source and subsequently mobility separatingions under a first pressure condition along a first axis; withmultidimensional IMS, at least one higher order IMS can receive ionsfrom the first IMS and subsequently mobility separating them under otherpressure conditions along axes that is orthogonal to the first IMS; andan MS having an interface receiving a section of mobility separated ionsfor mass analysis. Note that the MS does not necessary to be a TOFMS,the method shall apply to operating a multidimensional IMS with anyanalytical instruments.

Without a multidimensional IMS, the drift tube can also be operatedunder medium pressure; a similar effect on ion transportation efficiencyis expected. As shown in the figure, mobility separated ions areintroduced into a TOFMS in the direction that is perpendicular to theflight path of ions in the TOFMS. The initial energy difference effectto the TOFMS resolution is eliminated by accelerating ions into thedirection that is orthogonal to the sample inlet. Ions with a differentmobility may be introduced into the vacuum chamber simultaneously anddetected at different regions on the TOFMS detector without loss of ionmobility information. The spatial resolution on the detector can also beused for the ion identification based on both mass to charge ratio andion mobility, thus improving the systems detection specificity.

In a variety of embodiments, FIG. 15 shows a non-limiting example ofIMS-TOFMS configuration. In FIG. 15A, the vacuum inlet 1501 is shown asan array of pin-holes, however, the inlet could be a round orifice,pin-hole, or tubing, or a slit, or any other shape that could serve asthe barrier of vacuum and high pressure interface. In the shown example,the vacuum inlet has a shape that is similar to the projected profile ofmobility separated ion pockets. When ions are generated in the ionsource 1502 and introduced to the IMS via a inlet 1502 on one end,mobility separated ions pass through the field separator 1506, beingextracted from the extraction zone 1524 in the direction that isperpendicular to their drift direction 1522; therefore a larger sectionof the mobility separated ion pocket could be brought into theorthogonal interface 1508 of the TOFMS. Alternatively, mobilityseparated ions can be detected by a detector 1520 under high pressureconditions. Subsequently the ions are kicked into the ion accelerator1511 by repeller plate 1510 into the flight axis of the TOFMS anddetected at the TOFMS ion detector 1514; a reflectron 1512 could be usedfor improved TOFMS performance. In the specific example shown in FIG. 15A and B, the direction of the flight axis 1518 is parallel to the iondrift direction 1522. With a vacuum inlet having a shape that matchesthe side view cross section of ion pocket, orthogonally extracting ionsinto the MS provides a great benefit of ion transportation efficiencythrough the vacuum inlet. In general, when IMS ion outlet and TOFMS ioninlet (together shown as 1501 in FIG. 15B) matches, the TOFMS flightaxis 1518 and IMS drift axis 1522 can be arranged in any angle or anglesdepending on the instrument design needs, especially when a symmetricvacuum inlet, e.g. round, square, is used. With the example shown inFIG. 15, having the flight axis 1518 and drift axis 1522 arrangedsubstantially parallel (zero degrees) and/or anti-parallel (180 degrees)is preferred.

FIG. 16 illustrates a schematic diagram of an embodiment of the ionmobility spectrometer of the present invention. The sample is introducedto the spectrometer through a sample inlet 1600. The sample is ionizedwhile it passes through the ionization source 1602. The ionizationprocess is completed in the reaction region 1604 before reaching the iongate assembly 1606. In various embodiments, the ion mobilityspectrometer described herein can also sample chemicals in ionic formand/or from an external ionization source. The ion gate assembly 1606includes either a Bradbury-Nielsen gate or multiple grids that generatea narrow pulse of ions that is introduce into the drift region 1608.Both the reaction region 1604 and the drift region 1608 of the drifttube are guarded with ion guides.

The ion guides of the present invention are made of a single or aplurality helical coil of resistance wires. The coil of resistance wiresused in the reaction region and in drift region can be the same ordifferent coils. In prior art systems, the ion guides (or drift rings)are made of a series of rings with a wire attached to it. The lead wiresare brought to the outside of the drift tube and are connected to aseries of resistors that divide the drift voltage into multiple voltagedrop steps. The ion guide ring and resistor series in prior art systemsare replaced by a helical coil that is made of continuous resistancewire 1622 wrapped around a supporting frame 1624.

As shown in FIG. 16, the reaction 1604 and drift region 1608 areseparated by the ion gate assembly 1606. The reaction 1604 and driftregion 1608 can either share the same coil or use different coils. FIG.16 shows the coil in reaction region 1610 has large pitch between wires,which is designed to allow the drift gas to leak into the outer chamber,where it is pumped away from the gas outlet 1612. Using wires withdifferent resistivity in these two regions can control the time the ionsstay in a giving region. For example, in the reaction region 1604, theresistivity of coil can be lower than the resistivity of the coil in thedrift region 1608. In this example, the ions move at a relatively slowrate in the reaction region 1604, which allows the ions to havesufficient time for the ionization reaction to be completed. In someembodiments, the wire resistivities in both the reaction 1604 and thedrift region 1608 are optimized to generate the desired electric fieldstrength.

In other embodiments, the resistivities of the coils for drift 1608 andreaction 1604 regions can also be adjusted to heat these two regions todifferent temperatures, respectively. For example, when the drift tubeis interfaced to an electrospray ionization source, the reaction needsto be at a relatively higher temperature to assist in the desolvationprocess. In these embodiments, the resistance of the coil in thereaction region 1604 is made to be relatively high. However, if both alower voltage drop and a higher temperature are desirable in the region,then plural coils may be used in the reaction region 1604. The aboveexample shows an alternative embodiment where the drift 1608 andreaction 1604 region could be build with different coil configurations.

FIG. 17 illustrates an alternative embodiment of the drift tube of thepresent invention. The alternative embodiment shows a segmentedresistance coil that is used as an ion mobility drift tube. The sectionsof the coil are arranged in a similar fashion as the prior art driftrings.

FIG. 18 illustrates a three dimensional drawing of a rectangularresistance coil 1802 built from a single resistance wire 1806 supportedby a four-rod frame 1804. The size of the rod can be minimized to avoidcharge build up that may influence the electric field distributioninside the drift tube.

In some embodiments, the drift tube is made from multiple coils that arewrapped in opposite directions. Such coils can be formed by usinganother resistance wire that starts on the same rod as the existingwire, but that is wound in a counter clockwise direction. The wire willmeet the other wire on the bottom-left rod. As both of the coilscontinue, they will overlap at every half turn. In these embodiments,the magnetic field generated from the coil will be effectivelycancelled. The ion cyclotron motion under atmospheric pressure isnegligible for ion separation. However, under low pressure conditions,the effects from the magnetic field in a resistance coil based ionmobility spectrometer can be significant. In another embodiment,symmetric multiple reverse coils that overlap after a certain number ofturns are used to generate a more uniform electric field and caneliminate the effect of the magnetic field in the drift tube.

Depending on the drift tube design, the ion guide of the presentinvention can also be formed of a plurality of coils. FIG. 19illustrates a round drift tube comprising four resistance coils on asupporting frame 1900. The four coils 1902, 1904, 406, and 408 startedat the same level in the axis direction, but are offset by 90 degrees.Different numbers of resistance coils can be used depending on thedesired electric field uniformity requirements. In some embodiments, theelectric field uniformity is improved by increasing the number of coils.However, in these embodiments, material with higher resistivities isused in order to maintain the same level of power consumption. Theresistance coil can be formed in many different shapes depending on theframe design, such as round, rectangular, oval, or other polygons. Oneskilled in the art will appreciate that the resistance coil can beformed in an almost unlimited number of shapes.

FIG. 20A illustrates the radial cross sectional view of the four coildrift tube. In many embodiments, the same voltage is applied to all fourwires 2002, 2004, 2006, and 2008. The cross section view shows ions inthe center of the drift tube experience a symmetric electric field thatcauses the ions to drift along the axis similar to the conventional ionmobility spectrometer drift tubes. FIG. 20B illustrates an axial crosssectional view of the four coils. The four wires 2002, 2004, 2006, and2008 are separated with a distance that is chosen to prevent arcingbetween the wires. The distance is also optimized to shield the driftregion from outside electric fields.

After ions are introduced into the drift region 1608, the ions traveltoward the ion detection assembly 1614 under the influence of anelectric field. The ions are then detected as an ion current on thedetector matrix. During the time that the ions travel in the driftregion 1608, they are separated based on their ion mobility. The iongate assembly 1606 normally consists of a set of parallel wires whereadjacent wires in the set of parallel wires can be set to differentvoltages (Bradbury-Nielsen gate). The ion gate assembly 1606 may also bemade of two parallel grids that perform a push-pull type of ionextraction. An example of push-pull type ion extraction is setting thedownstream grid at a relatively low voltage and the upstream grid at arelative high voltage briefly during ion extraction. Ions between thetwo grids are then ejected into drift region 1608 in a pulse form. Insome embodiments, the downstream grid is replaced by a Bradbury-Nielsengate. The Bradbury-Nielsen gate can be opened for a shorter timeduration than the time duration that a higher voltage is applied on theupstream grid. In these embodiments, a combination of Bradbury-Nielsengate and push-pull type ion extraction generates a narrow pulse with ahigh ion density. The gate is used to control the ion pulse width.

The detector assembly consists of an aperture grid and a detectormatrix. FIG. 21B illustrates a detector matrix with multiple Faradayplates that is used to detect ions in an ion mobility spectrometeraccording to the present invention. The detector matrix illustrated inFIG. 21B is a segmented single Faraday plate. In the embodiment shown,the single Faraday plate is segmented into multiple Faraday plates in acircular design. The number of the segments depends on the desireddetector resolution.

Multiple coil ion mobility spectrometers use the detector matrix todetect spatially resolved ions in the radial direction under theinfluence of the radial direction electric field. The detector matrixcan also be used with an ordinary ion mobility spectrometer, which issimilar to Configuration A 2202 described in connection with FIG. 22, toselectively read out ion current at different radial locations. Theselective reading method can improve ion mobility spectrometerresolution by eliminating the effect of diffusion in the radialdirection and non-uniform electric field distribution close to drifttube wall.

For example, a resistance coil drift tube can be built using resistancewire of Iron Chrome Aluminum Molybdenum alloy that has electricalresistivity of 153 Microhms/cm.sup.3. When selecting a wire in “ribbon”form, with 0.035 mm in thickness and 0.08 mm in width, the wire hasresistance of 603 ohms/m. To build a drift tube of 2.54 cm i.d. and 4 cmtotal length, 32 meters of the resistance wire is needed (assuming thedrift electric field strength is 200 V/cm and the total powerconsumption is 33 W). Similarly, with the same material in round shape,0.05 mm in diameter, the resistance is 728 ohm/m. Assuming a 4 cm totaldrift length, 42.5 meters of resistance wire is used. The same driftfield of 200 V/cm is achieved and the total power consumption is 20 W.

As described herein, in one embodiment of the invention, a singleresistance wire may also function as a 33 or 20 W heater for thespectrometer. Such a heater will eliminate the heating element requiredin prior art conventional ion mobility spectrometers. In theseembodiments, the resistance coil functions as an electric field barrierto guard the drift 1608 and reaction 1604 region, and also as atemperature barrier that guarantees drift and reaction regiontemperature.

Referring to FIG. 16, the drift flow is introduced to the spectrometerat the drift gas inlet 1616 that is located behind the detector assembly1614. The drift gas enters the drift region 1608 (inside of theresistance coil) after being preheated. The resistance coil maintainsthe drift gas temperature after it enters the drift tube. As the driftgas flows toward the ionization source 1602, it also leaks out throughthe coil into the outer space between the resistance coil and thespectrometer housing 1618. If the resistance coil has a large pitch inthe reaction region 1604 as shown in FIG. 16, the majority of the driftgas exits from the reaction region 1604 section of the drift tube and ispumped away via the gas outlet 1612. Excessive sample and sample carriergas are also pumped away from the same outlet. Note that in analternative embodiment, the sample inlet 1600 can also be used as gasoutlet if the gas outlet 1612 is used as sample inlet. In order to usethe gas outlet 1612 as the sample inlet, a nonconductive tube needs tobe used to deliver samples to the inside of the resistance coil.

The drift tube of the present invention can be rapidly heated or cooleddown because of the low thermal mass construction. The drift tubetemperature is controlled by the drift gas pre-heater 1620 and theresistance coil. The drift tube of the present invention eliminates allceramic or glass tubing and other heavy and/or complex components. Thepre-heater 1620 shown in FIG. 16 directly exposes high temperatureheating wire to the drift gas. If the drift gas is recycled using aclosed loop wherein the inlet and outlet for the drift gas are connectedto form a circulatory gas system, the high temperature zone in thepre-heater 1620 may also be used to cause thermal decomposition ofcontaminants in the drift gas. Catalytic material may also be used inthe pre-heater 1620 for gas regeneration.

This invention eliminates the majority of the lead wires of the driftrings used in prior art conventional ion mobility designs. Theelectrical contacts that need to feed through the protective housing1618 are one high voltage power supply wire, a signal cable for thedetector matrix, and lead wires for ion gate assembly 1606. The ionmobility spectrometer of the present invention has relatively fewfeed-through devices. The protective housing 1618 can completely sealthe drift tube from the ambient conditions. By regulating the flow ofdrift gas and sample inlet/outlet, the ion mobility spectrometer canoperate under controlled pressure conditions.

In one embodiment, the resistance coil is segmented into multiplesections that are arranged sequentially to form a continuous constantelectric field in the reaction region or in the drift region. Themultiple resistance coils could be used to achieve the same performancefor rapid spectrometer heating and cooling, and other IMS operatingconditions. The segmented coils do not require using high resistancewires to form the coil as they could be interconnected using the voltagedivider circuit shown in FIG. 17. There is only a small voltage dropacross the segmented coils. The resistivity of the coil is only requiredto heat the drift tube. A voltage divider circuit 1702 is used to definethe drift field for ions traveling in the drift tube. FIG. 17 shows aportion of the drift tube that is made of segmented resistance coils1704, where an AC power supply 1706 is used to drive the coils. A highvoltage DC power supply 1708 is used to define the drift field through ahigh voltage divider circuits.

The ion mobility spectrometer of the present invention can operate undera continuous pressure gradient which achieves separation in both high(>2 V/cm-torr) and low (<2 V/cm-torr) field conditions. In low fieldconditions, the ion mobility is a constant for a given ionic species.However, the ion mobility is no longer constant under high fieldconditions. The mobility change vs. field condition characteristics(E/p, where E is the electric field strength and p is the pressure) isdependent on the particular ionic species being in the drift tube.Operating an ion mobility spectrometer in high field conditions canseparate ions that are inseparable in low field conditions.

The field condition is related to the drift field strength and to theoperating pressure. Scanning through a wide range of drift voltage isdifficult. In one embodiment, the ion mobility spectrometer of thepresent invention forms a continuous pressure gradient that generateslow/high field conditions which achieve maximum separation based on bothconstant and differential mobility of ions.

Drift field strengths in prior art ion mobility spectrometers are in therange of 200 V/cm to 500 V/cm depending on the size of the moleculesbeing separated. Using a drift field strength of 200 V/cm and pressurechanges from 760 torr to 1 torr, the E/p ratio changes from a low fieldcondition of 0.26 V/cm-torr to a very high field condition of 760V/cm-torr. To realize this operating condition, the pressure in thedrift tube needs to be pumped from ambient pressure to 1 torr, which canbe achieved using commonly available vacuum pumps.

It should be understood that the methods of operation described hereincan be applied to any ion mobility spectrometer having the ability toregulate the pressure to create low field and high field conditions. Thepresent invention is not limited to the ion mobility spectrometerdescribed in this invention having the resistance coil configurations.

In operation, samples are introduced into the spectrometer either bysample carrier gas flow or by direct electrospray of liquid samples inthe ionization/reaction region. The sample concentration normally lastsfrom a few seconds to a few minutes. During this period of time whensamples are continuously introduced into the instrument, the ionmobility spectrometer acquires significant number of spectra the sample.The pressure gradient may start synchronously or asynchronously with theion mobility spectra acquisition. Alternatively, the drift tube may beset to one or multiple pressure values that allow measuring ion mobilityin different field conditions.

The sample introduction at the sample inlet 1600 of the spectrometer maybe used as a trigger to start the data acquisition if a mechanicalvacuum pump is connected to the gas outlet 1612 as shown in FIG. 16 andboth the drift gas and the sample inlet flow are restricted to controlthe pressure in the drift tube. After a few moments of delay or afterthe target ions have been detected, the vacuum pump starts to reduce thepressure in the drift tube.

The mobility spectra can be plotted in a 3-D figure with ion mobility(K.sub.o) as x-axis, ion intensity as y-axis, and the number of spectraas z-axis. Traceable changes of a given ion mobility peak that are aconstant under low field conditions will be seen. The peak may start toshift as the time elapses (number or spectra in z-axis increase) and thedrift tube entering vacuum conditions. The curve that describes thisshifting function (projected on the x-z plane) can be used for chemicalidentification. The drift tube is typically designed to avoid thegeneration of arcs between the resistance coil and the surroundingelectrodes under the desired vacuum conditions. The distance betweenhigh voltage electrodes and the protective housing 118 (which istypically at ground potential) is chosen to reduce the probability ofgenerating an electrical discharge.

In one embodiment, a multiple resistance coil configuration of ionmobility spectrometer is arranged using concentric coils as shown inFIG. 21A. Given an inner coil 2103 having a constant voltage differencein the radial direction from the outer coil 2105 along the axis of thecoils, ions traveling between the coils experience a force from theelectric field in both the radial and the axial direction. Ions can beseparated in both the radial and the axial directions simultaneously,thus achieving two dimensional separation. The electric field strengthin the axial and the radial directions can be selected to achievesimultaneous high field 2107 and low field 2109 ion mobilitymeasurements.

FIG. 22 shows ion source outlet configurations of the ion mobilityspectrometer according to the present invention. Configuration A 2202introduces uniform ion population along the radial direction. The radialelectric fields are used to focus or de-focus the ion beam as theytravel through the drift tube. In Configuration B 2204, ions are pulsedinto the drift tube in a ring shape; with the radial electric forcepointing toward the center of the coil. The ions are separated whilethey are drifting down the drift tube as well as moving toward thecenter of the drift tube.

Referring back to FIG. 21B, the detector matrix 2102 detects the ioncurrent, and also detects the relative location toward the center of thedrift tube. Even though the figure only shows six elements 2104, 2106,2108, 2110, 2112, and 2114 in the detector matrix 2102, the matrix maycontain any desired number of rings so as to achieve the required radialmobility resolution. The ion motion under the influence of high and lowelectrical field conditions (E/p) is related to the ion drift conditionsin the drift tube, which includes electrical field strength, drift gasproperties, pressure, and temperature.

Configuration C 2206 shows another embodiment that achieves the twodimensional separation. In this case, the ions are introduced near thecenter of the drift tube. A de-focusing force is created with anelectric field in radial direction. Both ion intensity and location maybe detected on the detector matrix. The size and radial location of theion outlet apertures 2208 of the ionization source can be changed byadjusting the outer ring 2210 and inner disc 2212. The size is adjustedto balance the tradeoff between the resolution and the sensitivity for2D separation, i.e. reduce aperture size for higher resolution, andincrease aperture size for higher sensitivity.

A pulse of ions from the ionization source can either be generated usingconventional Bradbury-Nielsen ion gate configuration down stream fromthe ion outlet aperture 2208; or by using inner disc 2212 and outer ring2210 as shown in FIG. 22. The gate is closed by applying a voltageacross the outer ring 2210 and the inner disc 2212 and opened by setting2210 and 2212 at the same voltage. In this case, the gate assembly cangenerate ion pulses in the shape of a ring.

1. A drift tube for an ion mobility spectrometer comprising: a) at leastone dielectric structure component; and b) at least one ion guideelectrode that is affixed on the dielectric structure or structures,wherein the ion guide electrode or electrodes are arranged in a ringshape, a helical shape or serpentine shape.
 2. The drift tube of claim1, wherein the dielectric structure is made of aluminum nitride,beryllium oxide, fused silica, quartz, or alumina, having a shape of aflat plate, a curved plate, a round tube, a half round tube, a squaretube, or a rectangular tube.
 3. The drift tube of claim 1, wherein thedielectric structure has at least one substantially flat substrate. 4.The drift tube of claim 1, further comprises at least one electricalconductive leading contact in connection with the ion guidingelectrodes.
 5. The drift tube of claim 1, further comprises at least oneheating element.
 6. The drift tube of claim 5, wherein the heatingelement is mounted and/or affixed to the dielectric structure.
 7. Thedrift tube of claim 5, wherein the heating element is located on theother side of the dielectric material from the ion guide electrodes. 8.The drift tube of claim 5, wherein the heating element is adjacent tothe dielectric structure and in contact with the dielectric structure.9. The drift tube of claim 1, wherein the ion guide electrode is made ofconductive or resistive material.
 10. The drift tube of claim 9, whereinthe ion guide electrode is made of conductive material and is affixed ona cylindrical shape dielectric structure.
 11. The drift tube of claim 9,wherein the ion guide electrode is made of resistive material and isaffixed on a cylindrical shape dielectric structure.
 12. The drift tubeof claim 3, wherein the flat substrate has at least one electrode thathas a serpentine pattern.
 13. The drift tube of claim 11, wherein theion guide electrode has a helical shape.
 14. The drift tube of claim 11,wherein the ion guide electrode has a serpentine shape.
 15. The drifttube of claim 9, wherein the ion guide electrode is made of resistivematerial and is affixed on a flat dielectric structure.
 16. The drifttube of claim 15, wherein the ion guide electrode has a serpentinepattern.